This is an open-label, phase 1/2, multiple-indication platform study to explore safety, potential predictive immune-related biomarkers, and early efficacy (as measured by objective response rate \[ORR; Cohorts 1,2, 4,and 5\] and disease control rate \[DCR; Cohort 3\]) in patients with advanced or metastatic gastrointestinal (GI) tumors. Cohorts 1-4 are not randomized; however, Cohort 5 is comprised of two treatment arms to which patients are randomized in a 1:1 ratio.
The overall aim is to assess safety, predictive biomarkers, and preliminary efficacy as assessed by tumor response criteria at week 16 for cohorts1, 2, 3, and 4, and best overall response rate and OS in Cohort 5. If a cohort shows a promising ORR in Stage 1 of the Simon two-stage design, that cohort may be expanded to enroll additional patients (up to 50 patients in Cohorts 1 and 3 , up to 28 patients in Cohort 4, and up to 64 patients in Cohort 5) in an extension phase per predetermined statistical conditions. In addition, either or both arms of Cohort 5 may expand if the data collected in Stage 1 suggest that expansion may help in assessing the potential survival benefit of the investigational therapy(ies). In this study, we hypothesize that treatment with pelareorep will prime the tumor microenvironment (TME) for checkpoint blockade therapy, thereby increasing PD-L1 expression and the number of new T cell clones within the tumor, both of which are associated with increased response to checkpoint blockade.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
122
Pelareorep 4.5 x 10\^10 TCID50 via 1-hour IV infusion
Atezolizumab 840 mg IV infusion
Gemcitabine (1,000 mg/m2) and nab-paclitaxel (125 mg/m2)
Trifluridine/tipiracil administered at a 35 mg/m2 dose orally twice daily
mFOLFIRINOX- IV oxaliplatin 85 mg/m2; IV leucovorin 400 mg/m2; IV irinotecan 150 mg/m2; 5-FU 2400 mg/m2 by 46-hour infusion, per local standard of care
Nationales Centrum für Tumorerkrankungen Heidelberg
Heidelberg, Baden-Wurttemberg, Germany
RECRUITINGSLK-Kliniken Heilbronn GmbH
Heilbronn, Baden-Wurttemberg, Germany
RECRUITINGUniversitätsklinikum Tübingen
Tübingen, Baden-Wurttemberg, Germany
RECRUITINGUniversitätsklinikum Ulm
Ulm, Baden-Wurttemberg, Germany
RECRUITINGGemeinschaftspraxis Dr. Med Bernhard Heinreich
Augsburg, Bavaria, Germany
RECRUITINGKlinikum der Universität München
München, Bavaria, Germany
RECRUITINGHämatologisch-Onkologische Praxis Eppendorf
Hamburg, Hamburg, Germany
RECRUITINGAsklepios Kliniken Hamburg GmbH
Hamburg, Hamburg, Germany
RECRUITINGKrankenhaus Nordwest
Frankfurt am Main, Hesse, Germany
RECRUITINGSt. Josef-Hospìtal, Bochum
Bochum, North Rhine-Westphalia, Germany
RECRUITING...and 5 more locations
Overall Response Rate (ORR) for Cohort 1, 2, 4, and 5
Proportion of patients with complete response \[CR\], partial response \[PR\] assessed by the investigators and/or central reader according to RECIST v1.1
Time frame: At week 16 (within each cohort)
Disease Control Rate (DCR) - Cohort 3
DCR (complete response \[CR\], partial response \[PR\], and stable disease \[SD\]) assessed by the investigators according to RECIST v 1.1.
Time frame: at week 16
Overall Survival (OS) - Cohort 5
OS is defined as the time from date of first treatment to death from any cause
Time frame: Cohort 5: From the date of randomization through long term follow up at 2 years
Progression Free Survival (PFS)
Time from the first dose date of study treatment to the date of investigator-determined objective progression (according to RECIST 1.1) or death from any cause, whichever occurs first.
Time frame: From initiation of treatment to objective progression or death from any cause, whichever occurs first, up to two years
Duration of Response (DOR)
Time from documentation of the first CR or PR to the time of first documented evidence of progressive disease (or relapse for subjects who experience CR during the study) or death.
Time frame: From initiation of treatment to disease progression or death from any cause, whichever occurs first, up to two years
Disease Control Rate (DCR)
Overall DCR, defined as the number of patients with a best overall response of CR, PR, or SD according to RECIST v. 1.1.
Time frame: From initiation of treatment to disease progression or death from any cause, whichever occurs first, up to two years
Overall Response Rate (ORR) - Cohort 1-4
ORR, defined as the percentage of patients with a best overall response of complete response \[CR\] or partial response \[PR\] according to RECIST v 1.1, and confirmed ORR, defined as the percentage of patients with a CR or PR at two or more consecutive evaluation timepoints.
Time frame: From initiation of treatment to disease progression or death from any cause, whichever occurs first, up to two years
Overall Survival (OS) - Cohort 1-4
OS defined as the time from date of first treatment to death from any cause
Time frame: From the date of randomization through long term follow up at 3 years
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